Sterile Product . . . . . . . . .

Are dosage forms of therapeutic agents that are free of viable

microorganisms.

Parenterals

Opthalmics

Irrigating preparations

What are perenterals ?

Are sterile, pyrogen free preparations injected through skin or mucous

membrane into internal body compartments.

• Para Enteron: Para means without Enteron means Intestine

History Of Parenteral Therapy

1657: First recorded injection in animals
Sir Christopher Wren

1855: First subcutaneous injections of drugs using hypodermic needles

Dr. Alexander Wood

1920s: Proof of microbial growth resulting in infections

Dr. Florence Seibert

1926: inclusion in the National Formulary

1946: Organization of Parenteral drug Association

1965: Development of Total Parenteralnutrition(TPN)

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 • 1982: Insulin and biotechnology products
• Infusion pumps

Routes Of Parenteral Administration

Intradermal (I.D.): Injections into the superficial layer of skin. Only
small volumes (0.1 ml) can be used. Absorption is slow by this route.

Subcutaneous (S.C., S.Q., Sub-Q, Hypo): Injections into

the loose tissue beneath the skin. Absorption is faster than intradermal

Intramuscular (I.M.): Injections into a muscle mass up to 5 ml can

be given

Intravenous (I.V.): Injection into a vein. There is little limitation on

volume and absorption in instantaneous.

Intracardiac: -Injections into heart chamber.

Intrathecal (spinal fluid): Injection into spinal fluid.

Intrasynovial:- (joint fluid area): Injection into a joint fluid area.

Intra-articular:- Injections into a joint. This method is used for

arthiritis and joint injuries.

Disadvantages Of Parenteral Administration

Administered by trained personnel only using aseptic procedures

Pain on injection

Difficult to reverse an administered drug’s effects

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 Manufacturing and Packaging requirements

Cost

Advantages Of Parenteral Administration

Fastest method of drug delivery (e.g. cardiac arrest, asthama, shock)

Viable alternative to unsuccessful oral therapy

Less patient control (I.e. return visits)

Local effect (e.g. dentistry, anesthesiology)

Prolonged action (e.g. intra- articular steroids, IM penicillins)

Correcting serious fluids and electrolyte imbalance

Total Parenteral Nutrition (TPN)

General Requirements
Production in clean areas

Separate areas for operations

component preparation

product preparation

filling etc

Level of cleanliness

Filtered air

Laminar air flow:

air speed (horizontal versus vertical flow)

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 number of air changes

air samples

Premises
Design

avoid unnecessary entry

Clean areas

smooth, unbroken surfaces

permit cleaning

no uncleanable cupboards, equipment

ceilings

sinks and drains

Changing rooms

designed as airlocks

flushed with filtered air

separate for entry and exit desirable

hand washing facilities

visual and/or audible warning system

Personnel
Outdoor clothing

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 Appropriate to air grade

Grade D

hair, beard and shoes

Grade C

hair and beard

suit covering wrists, neck

no fibres

Grade B

masks, gloves

Laundry and changes

Minimum number in clean areas

aseptic processing

inspection and control

Regular training

manufacture

hygiene

microbiology

outside staff

Hygiene and cleanliness

contaminants

SOPs : Changing and washing

Equipment

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 Air supply:(HVAC)

Generation and supply of filtered air

Airflow patterns

Pressure differentials monitored and recorded

Conveyer belts

Effective sterilisation of equipment

Maintenance and repairs

Planned maintenance, validation and monitoring

Processing
Minimise contamination

No unsuitable materials e.g. live microbiological organisms

Minimise activities

staff movement

Temperature Control

Finishing Of Products
Checks for integrity

Maintenance of vacuum (where applicable) checked

Parenteral products: Individual inspection

background

eyesight checks

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 breaks

Vehicles For Injection

AQEOUS VEHICLE
Frequently, isotonic (to blood) to which drug may be added at the time of

use.

Water-miscible Vehicle
Portion of the vehicle in the formulation

Used primarily to effect solubility of drugs and / or reduce

hydrolysis

Ethyl alcohol; polyethylene glycol(liquid) and propylene glycol

Non Aqueous vehicles:

Fixed oils (Vegetable origin ,liquid , and rancid resistance ,

unsaturation, free fatty acid content) used in hormone preparations

Examples of Water-Miscible Vehicles

Aqueous Co solvent vehicles:

ethyl alcohol (Alcohol USP)

propylene glycol

Glycerin USP

Polyethylene glycol 300 NF

Examples of Non aqueous vehicles

Oleoginous Vehicles

Peanut Oil

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 Corn Oil

Cotton seed Oil (Depo –Testosterone R- Upjohn)

Sesame oil

Soyabean oil (source of fat in intralipid R)

Ethyl oleate

Isopropyl myristate

Parenteral Added Substances

Antibacterial agents

Prevent the multiplications of microorganisms

Antioxidants

Prevent oxidization of drugs

Buffers

Prevent degradation

Adjusted to physiological pH when administered

Tonicity contributors

often buffer salts, provide patient comfort

Antibacterial agents
Limited concentration of agents

Phenylmercuric Nitrate 0.01%.

Benzalkonium chloride 0.01%

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 Phenol or cresol 0.5%

Chlorobutanol 0.5%

Refrigeration slows the growth, does not prevent Antibacterial agents

testing.

Antioxidants
Prevent the oxidation by being oxidized faster than the drug or by blocking

oxidization

Water soluble: acid, sodium bisulfate, sodium metabisulfite, sodium sulfite

Oil soluble: Butylated hydroxytoluene (BHT), Butylated hydroxyanisole

(BHA)

Buffers
Added to maintain the pH

Result in stability

Effective range, concentration, chemical effect

Examples:

Sodium Citrate and citric acid

Sodium Acitate and Acitic acid

Sodium Benzoate and Benzoic acid

Sodium tartrate and tartaric acid

Sodium Phosphate (Monobasic Sodium hydrogen phosphate (NaH2PO4

and Dibasic Sodium Hydrogen Phosphate)

Sodium Bicarbonate

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Tonicity Agents
Reduce pain of Injection

Can include buffers

Sodium chloride

Potassium chloride

Dextrose

Mannitol

Sorbitol

lactose

Unique Characteristics Of Parenterals

Sterile

Particle Free

USP microscopic methods for large –volume parenterals

not more than 50 particles/ml that are equal to or larger than 10

micrometers and not more than 5 particles/container that are equal

to or larger than 25 micrometers

Not more than 10,000 particles/container that are equal to or larger than 10

micrometers and not more than 1000 particles/container that are equal to

larger that 25 micrometers.

Pyrogen free (if parenteral)

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 Pyrogen Test

Traditional tests uses rabbits, solution injected ear vein (n= 3) or

washing from a sterile device

Measure body temperature

LAL TEST: Simpler, rapid and greater sensitivity test than the pyrongen

test Limulus amoebocyte lysate of (limulus polyphemus) from the hoarse

shoe crab.

Contain a protein that clots with the presence of Bacterial

endotoxins.

Packaging, Labeling And Storage Of Injections

Multiple – dose container

Single dose container (ampules and vials)

Types of Glass

Type I, Boroslicate glass

Type II, soda-lime treated glass

Type III, a soda-lime glass

NP, Soda-lime not suitable for parenterals

Rubber closures

Labels : Name, Percentage, Route of administration, Storage

condition, Manufacturer, Lot number.

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Available Injections
Small Volume Parentrals (25-50ml)

Large volume Parentrals

Parenteral Incompatibility
Physical

Chemical

Therapeutic:

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